ArticleAutophagy2024
Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 332 papers.
What it found
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Who cites it
332 citing papers in PubMed, 352 citations in OpenAlex.
- Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights.Genes & diseases · 2027Review
- Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.Genes & diseases · 2026Review
- Lactylation-Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate-H3K18la-RPL11 Axis Drives Gemcitabine Resistance in Pancreatic Cancer by Integrating Protein Synthesis and DNA Damage Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TFAM loss drives oxaliplatin resistance by linking mtDNA release to STING-TBK1-mediated lysophagy.Oncogene · 2026Article
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- OLR1 promotes cell proliferation and invasion while represses apoptosis via regulating histone H3 lysine 18 lactylation‑mediated LEMD1 in papillary thyroid cancer.Oncology reports · 2026Article
- Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases.Clinical and translational medicine · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Combined Anti-PD-1/PD-L1 and Anti-angiogenic Therapy: An Emerging Direction for Future NSCLC Treatment.Current treatment options in oncology · 2026Review
- Review
- LncRMRP drives bladder cancer invasion via a lactylation-driven positive feedback circuit.Oncogene · 2026Article
- Article
- Histone modifications: mechanisms, metabolic regulation, and therapeutic targeting in cancer.Precision clinical medicine · 2026Review
- Lactylation-related prognostic signature characterized in pancreatic ductal adenocarcinoma through public scRNA-seq dataset and machine learning algorithms: the TOP2A-H3K18la-NQO1 axis orchestrates malignant progression.British journal of cancer · 2026Article
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Autophagy Orchestrates Anti-Tumor Immunity to Enhance Chemosensitivity via the FBXW2/C/EBPβ/TIMP-2 Axis in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
272 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.